Back-scattering interferometry (“BSI”) takes advantage of the multitude of light/sample interactions occurring every time a measurement is made. Described in U.S. Pat. No. 5,325,170 (Bornhop et al., Jun. 28, 1994), BSI is therefore one of the most sensitive analytical techniques and can be performed with extremely low sample concentrations and/or sample volumes. The last decade has seen a tremendous amount of growth in BSI technology. For example, U.S. Pat. No. 7,130,060 (Bornhop et al., Oct. 31, 2005) describes a method for determining absolute refractive index (RI) using BSI in which light is directed at a capillary tube and refractive index is determined as a function of the angle at which there is a marked change in intensity. Bornhop et al. (Science (2007) 317: 1732) describes a free-solution, label-free molecular interactions investigated by BSI. U.S. patent publication 2009-0185190 (Weinberger et al., Jul. 23, 2009) describes an interferometer for detecting analyte in a microfluidic chip. The device maintains a stable temperature at the chip with variation of no more than 0.005° C. and/or no more than 0.020° C. in the medium through which the optical train travels from a source of coherent light to the chip when ambient temperature changes up to 5 degrees centigrade over five minutes. The device comprises thermally isolated compartments that hinder heat transfer from one part of the instrument to another and temperature regulators that regulate temperature of the chip and the optical train compartment as a function of temperatures at the chip, in the compartment, and ambient.
Despite these advances, BSI measurements continue to suffer from several disadvantages—mainly related to eliminating sources of noise that would be irrelevant in less sensitive techniques. Recently developed methods utilizing refractive indices can require either the use of sequential measurements or the use of separate control measurements, such as in an adjacent capillary. The accuracy of such sequential or separate measurements can be less than ideal due to, for example, temperature changes that exist between measurements or between the optical properties of adjacent capillaries.
Accordingly, there is a need in the art for methods, systems, and apparatuses that can provide multiple refractive index related measurements simultaneously or substantially simultaneously without complications from, for example, thermal or pressure variations between sample and reference environments.